MALAT1 is a conserved long noncoding RNA whose expression correlates with many human cancers. However, its significance in immunity remains largely unknown. Here, we observe that MALAT1 is upregulated in lipopolysaccharide (LPS)-activated macrophages. Knockdown of MALAT1 increases LPS-induced expression of TNFa and IL-6. Mechanistically, MALAT1 was found to interact with NF-jB in the nucleus, thus inhibiting its DNA binding activity and consequently decreasing the production of inflammatory cytokines. Additionally, abnormal expression of MALAT1 was found to be NFjB-dependent. These findings suggest that MALAT1 may function as an autonegative feedback regulator of NF-jB to help fine-tune innate immune responses.
Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1) but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24) which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.
Landslide hazard prediction is a difficult, time-consuming process when traditional methods are used. This paper presents a method that uses machine learning to predict landslide hazard levels automatically. Due to difficulties in obtaining and effectively processing rainfall in landslide hazard prediction, and to the existing limitation in dealing with large-scale data sets in the M-chameleon algorithm, a new method based on an uncertain DM-chameleon algorithm (developed M-chameleon) is proposed to assess the landslide susceptibility model. First, this method designs a new two-phase clustering algorithm based on M-chameleon, which effectively processes large-scale data sets. Second, the new E-H distance formula is designed by combining the Euclidean and Hausdorff distances, and this enables the new method to manage uncertain data effectively. The uncertain data model is presented at the same time to effectively quantify triggering factors. Finally, the model for predicting landslide hazards is constructed and verified using the data from the Baota district of the city of Yan’an, China. The experimental results show that the uncertain DM-chameleon algorithm of machine learning can effectively improve the accuracy of landslide prediction and has high feasibility. Furthermore, the relationships between hazard factors and landslide hazard levels can be extracted based on clustering results.
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